Table 1.
Recent developments of drug-loaded NPs for topical treatments of skin diseases.
| Nanocarriers | NPs Parameters | Drug Loaded | Skin Permeation Studies | Ref |
|---|---|---|---|---|
| therapy of psoriasis | ||||
| NLCs (Precirol VR ATO 5, LabrafacTM PG, TweenVR 20) |
203.3 ± 1.20 nm; PDI 0.29 ± 0.04; EE% 100% |
dithranol | IMQ induced a murine model of human psoriasis | [358] |
| liposomes (DOTAP + CHl) |
111 ± 1.62 nm; PDI 0.27 ± 0.08; EE% 93 ± 2.12%; ZP 41.12 ± 3.56 mV |
cyclosporine | IMQ induced a murine model of human psoriasis | [359] |
| 1-liposomes (PC + CH), 2-niosomes (Span 80 + CH), 3-emulsomes (PC + CH + tristearin) |
1-(368.5 ± 43 nm, PDI 0.136 ± 0.024, EE% 70.98 ± 2.36%); 2-(342.7 ± 35 nm, PDI 0.167 ± 0.045, EE% 54.30 ± 2.16%); 3-(172.8 ± 10 nm, PDI 0.116 ± 0.019; EE% 83.79 ± 3.58%) |
capsaicin | hairless albino rat skin from the abdominal and dorsal area after removing underlying fat and subcutaneous tissues | [360] |
| liposomes (PC + OA), (PC + CH) |
80–140 nm; PDI 0.14−0.37; ZP 6.64–2.56 mV; EE mol% 2.41–10.20% |
methotrexate | the abdominal skin of newly born pig, the hairs, and lipid layer were removed | [361] |
| niosomes (Span 60 + CH) |
477.8 nm; EE% 83.02% |
diacerein | in vitro-the albino rats; the hairs, and subcutaneous tissues were removed | [362] |
| niosomes (Span 60 + CH) |
369.73 ± 45.45 nm; EE% 90.32 ± 3.80%; ZP −36.33 ± 1.80 mV |
acitretin | ex vivo- HaCaT cells (a keratinocyte cell line); in vivo-mouse tail model |
[363] |
| niosome hydrogels (Span 20, Span 60, CH) |
147.4 nm ± 5.6 nm; PDI 0.258 ± 0.02; ZP 48.9 mV ± 1.1 mV; Y% 90.42% ± 3.38%. | celastrol | female C57/BL6 mice, the dorsal hair was removed (a razor + depilatory cream) | [364] |
| ethosomes (soya lecithin + ethanol) |
376.04 ± 3.47 nm; EE% 91.77 ± 0.02% | methotrexate + salicylic acid | ex-vivo-pig ear skin; in vivo-the shaved dorsal surface of Albino mice | [365] |
| ethosomes, liposomes | 116 to 199 nm (liposomes); 146 to 381 nm (ethosomes); EE% ≥ 97.2% (liposomes), ≥77% (ethosomes) |
anthralin (1,8-dihydroxy-9-anthrone) | in vitro-a dialysis membrane (MWCO: 6–8 kDa); ex vivo-Wistar male albino rats with abdominal skin freed from hair; the connective tissue, fat, and subcutaneous tissues | [366] |
| cationic liposomes (DC-CH, CH), anionic liposomes (egg lecithin, CH, tetramyristoyl cardiolipin) |
100 nm; ZP + 25.8 mV, EE% 75.12% (cationic); ZP −28.5 mV, EE% 60.08% (anionic) | psoralen + UVA (PUVA) | IMQ-induced psoriatic plaque model | [367] |
| nanoemulsion | 202.6 ± 11.59 nm; PDI 0.233 ± 0.01; EE% 76.57 ± 2.48% |
methotrexate | in vivo, in vitro: male rabbits, male Sprague Dawley rats; the abdomen skin cleaned of lipids and connective tissues | [368] |
| nanoemugel | 76.93 nm; PDI 0.121; ZP −20.5 mV |
Curcumin + imiquimod |
ex vivo, in vivo-BALB/c mice; the abdominal, and the dorsal skin hair shaved, the subcutaneous tissue, and fat at the dermis removed | [369] |
| nanoemusion | 93.37 ± 2.58 nm; PDI 0.330 ± 0.025. | tacrolimus and kalonji oil | in vitro-a dialysis bag membrane with a molecular weight cut-off 12,000 Da; in vitro-A-431 cell lines; ex vivo-the dorsal portion of pig ear skin shaved; subcutaneous fat removed; in vivo-IMQ induced psoriasis model on BALB/c mice shaved on their back | [370] |
| the nanomiemgel composed of nanomicelle-NMI (with Vit.E TPGS) + nanoemulsion – NEM (olive oil + miglyol + Polysorbate80 + Transcutol) |
229 ± 16 nm (NEM); 185 ± 10 nm (NMI); PDI 0.18 ± 0.06 (NEM); PDI 0.12 ± 0.08 (NMI); EE% 96.74 ± 4.24% (ACE-NEM); EE% 95.72 ± 3.58% (CAP-NEM); NMI, 94.88 ± 3.76% (ACE-NMI); 92.69 ± 3.08% (CAP-NMI) | aceclofenac (ACE) capsaicin (CAP) |
ex vivo-human skin with a thickness of 0.5–0.1 mm; in vivo-C57BL/6 mice with shaved backs |
[371] |
| liposomes (DDC642) | 100 nm | RNA interference (RNAi) molecule | in vitro-psoriasis-induced keratinocytes, and melanocytes cultured | [372] |
| transfersomes |
94.49 ± 6 nm–154.65 ± 8.46 nm; EE% 59.17 ± 5.03% |
tacrolimus | ex vivo, in vivo-Albino Wistar Rat, the hairs trimmed | [373] |
| flexible liposomes (lecithin, Tween-80) |
76.1 ± 0.5 nm; PDI 0.251 ± 0.009; EE% 99% |
all-trans retinoic acid, betamethasone | in vitro-immortalized human keratinocytes (HaCaT), full-thickness skin from the ventral part of rats with removed extraneous subcutaneous fat; in vivo-BALB/c mice model induced by IQM |
[374] |
| polymeric NPs (PLGA) |
307.3 ± 8.5 nm; PDI 0.317; ZP −43.4 ± 2.6 mV; EE% 61.1 ± 1.9%; DL 1.9 ± 0.1% | apremilast | male Wistar albino rats | [375] |
| PLGA NPs | 100 nm | indomethacin | rat skin/iontophoresis | [376] |
| polymeric micelles (poly(ethylene glycol)-b-oligo(desaminotyrosyl-tyrosine octyl ester suberate)-b-poly(ethylene glycol) |
70 nm; PDI ≤ 0.22 | paclitaxel | HaCaT (a cell line of human keratinocytes); human cadaver skin samples |
[377] |
| polymeric micelles (methoxy-poly(ethylene glycol)-dihexyl substituted polylactide (MPEG-dihexPLA) diblock copolymer) | 10–50 nm | tacrolimus | human skin | [378] |
| polymeric nanocapsules (Eudragit RS 100) |
139 ±3.6 nm; ZP +11.38 ± 1.7 mV; EE% 81 ± 2% |
dexamethasone | in vitro | [379] |
| Nanospheres; lipoglobules |
70 nm | thymoquinone | in vitro-cell lines and IMQ-induced psoriatic plaque model |
[380] |
| biogenically obtained Au-NPs (ethanolic extract of Woodfordia fruticosa flowers) | 10–20 nm | myricetin quercetin ellagic acid |
in vivo-Swiss albino mice, IMQ-induced psoriasis-like skin inflammation model; shaved dorsum surface of the mice skin | [381] |
| Au-NPs functionalized by 3-mercapto-1-propansulfonate (AuNPs-3MPS) |
5 nm | methotrexate | in vivo-C57BL/6 mice (Charles River) with shaved backs; in vitro-acute toxicity studied on human skin equivalents (HSEs) after 21-day culture period (adult human keratinocytes seeded on a dermal substitute consisting of a collagen type I matrix and fibroblasts) | [382] |
| therapy of vitiligo | ||||
| liposomes (DC-CH, CH + sodium deoxy cholate) |
120–130 nm; ZP +46.2 mV; EE% 74.09% (psoralen), 76.91% (resveratrol) | psoralen, resveratrol | B16F10 cell line | [383] |
| deformable liposomes | 64.8 ± 1.3 nm; PDI 0.14 ± 0.03; ZP −27.0 ± 1.1; EE% 82.7 ± 0.4 (baicalin); 61.1 ± 1.4 nm; PDI 0.24 ± 0.01; ZP −38.1 ± 1.4; EE% 87.1 ± 1.2 (berberine) | baicalin, berberine | ex vivo-the epidermis (thickness ~200 μm) from newborn pig; in vitro-human immortalized keratinocytes (HaCaT) |
[384] |
| elastic cationic niosomes (Tween61/CH/dodecyldimethyl ammonium bromide) |
163.5 ± 1.8 nm; ZP (+) 37.0 ± 0.6 (PE); 101.5 ± 0.5 nm; ZP (+) 36.1 ± 7.1 (TPE) |
human tyrosinase plasmid (PE) Tat/human tyrosinase plasmid (TPE) |
the melanoma (B16F10) cell | [385] |
| microemulsion | 18.26 nm | clobetasol propionate | in vivo-human | [386] |
| ethosomes | 80 ± 1.2 nm; ZP −0.531 ± 0.10 mV; EE% 99.14 ± 0.32% |
methoxsalen | ex vivo, in vivo-shaved skin of Wistar rats | [387] |
| therapy of alopecia | ||||
| chitosan nanoparticles | 235.5 ± 99.9 nm; PDI of 0.31 ± 0.01; ZP +38.6 ± 6.0 mV |
minoxidil sulphate | in vitro-porcine ear skin | [388] |
| NLCs | 393.5 ± 36.0 nm; PDI < 0.4; ZP +22.5 ± 0.2 mV; EE% 86.9% (minoxidil), 99.9% (latanoprost) | minoxidil + latanoprost | in vitro-porcine ear skin | [389] |
| polymeric nanocapsules (poly-ε-caprolactone) /manual massage |
197.8 ± 1.2 nm; PDI 0.15 ± 0.01; ZP −30.1 ± 1.8 mV; EE% 93.9 ± 0.4% | latanoprost | in vitro-the full-thickness skin of the porcine ears | [390] |
| NLCs (stearic acid + oleic acid) |
281.4 ± 7.4 nm; PDI 0.207 ± 0.009; ZP −32.90 ± 1.23 mV; EE% 92.48 ± 0.31%; DL 13.85 ± 0.47% |
minoxidil | in vitro-the abdominal full-thickness skins of male Sprague Dawley rats | [391] |
| polymeric NPs | 90–300 nm | minoxidil | C57BL/6 mice | [392] |
| PLGA nanospheres | 182–205 nm | hinokitiol, glycyrrhetinic acid, 6-benzyl-amino- purine |
in-vitro, in-vivo -C3H mice, extracted human scalp skin |
[393] |
| cationized gelatin microspheres |
- | Tbx21 siRNA | in vivo-C3H/HeJ mice, a mouse model of alopecia areata; ex vivo-skin samples obtained from the peripheral region of the alopecic skin of patients |
[394] |
| liposomes (saturated phospholipid + CH) |
6.1 ± 1.8−16.6 ± 3.4 µm; PDE 88.6% |
finasteride | in vitro-the full-thickness abdominal, and the dorsal mice skin after hair, and subcutaneous fat removal | [395] |
| therapy of acne | ||||
| Liposomes (egg PC + CH) | 120 nm; ZP −43 mV | lauric acids (anti-Propionibacterium acnes (P. acnes) | in vitro, in vivo-a mouse ear model | [396] |
| SLNs | 180 ± 2 nm; ZP 47 ± 4; EE% 100 ± 1% | retinoic acid | in vivo-a mutant strain of hairless mouse (rhino mice) | [397] |
| niosomes | - | benzoyl peroxide, clindamycin | in vivo-110 patients | [398] |
| therapy of skin cancer | ||||
| cationic lipid NPs (CTAB + stearic acid + monoolein) |
196.90 ± 39.73 nm; PDI 0.26 ± 0.02; ZP +63.85 ± 12.37 mV; EE% 47.39 ± 2.52% | doxorubicin | in vitro-the pig ears skin with removed hair; in vivo-female nude BALB/c/iontophoresis | [399] |
| cationic liposomes/iontophoresis | 192.6 ± 9.0 nm; PDI 0.326 ± 0.004; ZP 56.4 ± 8.0 mV; EE% (curcumin) 86.8 ± 6.0% |
curcumin + STAT3 siRNA | in vitro-mouse melanoma cells (B16F10), ex vivo-porcine ear skin; in vivo- C57BL/6 mice | [400] |
| liposomes (lipoid S75 + oleic acid) |
79.0 ± 4.1 nm; PID 0.12; ZP 40.06.7 mV; EE% 71.2 ± 10.9% (QUE); 72.1 ±6.6% (RSV) |
quercetin (QUE)+ resveratrol (RSV) | in vitro-human dermal fibroblasts culture; in vivo-female CD-1 mice with the back skin shaved |
[401] |
| Immunoliposome /iontophoresis |
137 ± 25 nm; PDI 0.26 ± 0.04; ZP −6 mV |
5-fluorouracil+ cetuximab | in vitro-A431 (EGFR positive) and B16F10 (EGFR negative) cell lines; in vitro- dermatomed skin of the outer portion of porcine ears; in vivo-immunosuppressed Swiss nude mice | [402] |
| Au-NPs | 55.1 ± 5.1 nm; ZP −15 ± 1 mV |
phytochemicals present in Vitis vinifera seeds | in vitro-A431 cancer cell line (skin carcinoma, human); HaCaT (normal, human immortalized keratinocyte cell line) | [403] |
| Fe2O3-NPs | 10 ± 2.5 nm; ZP 7.9 ± 0.4 mV | epirubicin | in vitro-melanoma WM266cells; ex vivo-human cadaver skin without subcutaneous fat |
[404] |
| polymeric NPs with EGFR antibody/photodynamic therapy | - | indocyanine green | in vitro-shaved the dorsal skin area of the Female CD1 mice | [405] |
| poly (lactic-co-glycolic acid) NPs | 130.4 ± 10.5 nm; PDI 0.095; EE% 52 ± 3.34% |
bromelain | in vivo-Male Swiss albino mice | [406] |
Abbreviations: polydispersity index (PDI); soya phosphatidylcholine (PC); cholesterol (CH); the entrapment efficiency (EE%); N-(1-(2,3-dioleoyloxy) propyl)-N, N, N-trimethylammonium chloride (DOTAP); phosphatidylcholine (PC); oleic acid (OA); zeta potential (ZP); entrapment efficiency (%EE); drug loading (%DL); poly-(D,L-lactide-coglycolide) (PLGA); imiquimod (IMQ); trans-activating transcriptional (Tat,T); drug loading (DL); percent drug entrapment (PDE); cetyltrimethylammonium bromide (CTAB); conjugated epidermal growth factor receptor (EGFR).